Substance use comorbidity is among the most frequent and disabling problems experienced by persons with schizophrenia, and a key treatment priority for NIDA. As many as 65% of people with schizophrenia experience significant problems with substance use, most frequently cannabis, and these individuals have the worst course, outcomes, and quality of life. While advances in integrated psychiatric and substance use treatment and specific behavioral interventions for people with severe mental illness have led to better standards of care, remarkably few effective treatments exist that specifically target the unique needs of individuals with schizophrenia and comorbid substance use problems. Impairments in cognition and affect regulation, currently unresponsive to pharmacotherapy, are major contributors to the exceedingly high rates of cannabis and other substance misuse in schizophrenia and highlight the need for targeted cognitive and affective remediation programs for this population. To date, however, no cognitive remediation approach has been adapted to the unique needs of schizophrenia patients with significant substance use comorbidity. In response to RFA-DA-10-007, "Cognitive Remediation Approaches to Improve Drug Abuse Treatment Outcomes," we propose to take the first step in integrating, adapting, and preliminarily testing a cognitive remediation (Cognitive Enhancement Therapy [CET]) and affect regulation (Personal Therapy [PT]) intervention for cannabis misusing patients with schizophrenia. Both of these psychosocial interventions have been rigorously tested in large samples of individuals with schizophrenia who do not experience substance use problems, and have been shown to be highly effective at remediating the untreated cognitive and affective impairments that can lead this population to use drugs. This project will now integrate and adapt these interventions, and conduct an initial examination of their feasibility, acceptability, and efficacy in a sample of 32 schizophrenia patients with significant cannabis use problems, the most frequent drug of abuse in this population. Patients will be randomized to CET/PT plus treatment as usual (TAU) or TAU alone and treated for 18 months. Treatment adherence, attendance, and satisfaction data will be collected throughout the trial to assess the feasibility and acceptability of CET/PT for cannabis misusing schizophrenia patients. In addition, comprehensive assessments of substance use, functioning, cognitive, and affective outcomes will be administered prior to treatment, and at 9 and 18 months, to estimate the efficacy of CET/PT on critical outcomes. It is expected that the findings from this project will provide strong support for the acceptability, feasibility, and efficacy of CET/PT for cannabis misusing schizophrenia patients that will justify the conduct of a more definitive trial and ultimately result in a significant treatment advance for the many individuals with schizophrenia who experience comorbid substance use problems. PUBLIC HEALTH RELEVANCE: The use of drugs, most commonly cannabis, is a frequent and highly disabling problem in schizophrenia that places a significant burden on society, and for which few effective treatments exist. Underlying these problems are untreated impairments in cognition and affect regulation, which drive many patients to use drugs. This project is of significant public health relevance in that it proposes to bring an evidence-based cognitive remediation (Cognitive Enhancement Therapy) and affect regulation (Personal Therapy) intervention to bear on this major public health problem, in an effort to advance the treatment of significant substance use comorbidity in schizophrenia and reduce the burden of these disorders on the individuals who suffer from them, their families, and society.